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Molecules
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Oxidative Stress and Antioxidants in Degenerative Conditions
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Oxidative Stress and Antioxidants in Degenerative Conditions

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Medicinal Chemistry".

Deadline for manuscript submissions: 31 August 2026 | Viewed by 2219

Special Issue Editors

Prof. Dr. Eleni A. Rekka

E-Mail Website
Guest Editor
Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
Interests: drug design and synthesis and mechanism of action; structure/activity relationships. free radicals; oxidative stress and antioxidant agents; anti-inflammatory compounds; hypolipidemic agents; multi-targeting compounds; neurodegenerative conditions; xenobiotic metabolism
Dr. Panagiotis Theodosis-Nobelos

E-Mail Website
Guest Editor
Department of Pharmacy, School of Health Sciences, Frederick University, Nicosia 1036, Cyprus
Interests: antioxidants; oxidative stress; anti-inflammatory compounds; hypolipidemic agents; multi-targeting compounds; neurodegenerative conditions; cyclooxygenase inhibition; lipoxygenase inhibition

Special Issue Information

Dear Colleagues,

Oxidative stress, characterized by an imbalance between the production of reactive oxygen species (ROS) and the body's ability to neutralize them, has been implicated in a wide range of chronic diseases, including cardiovascular diseases, neurodegenerative disorders, diabetes, and cancer. However, antioxidants play a crucial role in mitigating oxidative damage by scavenging free radicals and preserving cellular integrity. Understanding the mechanisms underlying oxidative stress and the protective actions of antioxidants is essential for developing effective therapeutic strategies and preventive measures to address degenerative disorders and conditions.

This Special Issue aims to engage a broad audience interested in the latest developments in the field of antioxidants and oxidative stress. By providing a platform for the dissemination of high-quality research and expert opinions, we aim to foster collaboration and enhance knowledge in this critical area.

We invite the submission of original research articles, reviews, and perspectives that explore the role of antioxidants and oxidative stress in neuronal and peripheral degenerative diseases. Submissions should align with the scope of the Special Issue and provide novel insights or significant contributions to the field. All submissions will undergo a rigorous peer-review process to ensure the highest standards of scientific quality.

Prof. Dr. Eleni A. Rekka
Dr. Panagiotis Theodosis-Nobelos
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • antioxidants
  • oxidative stress
  • chronic-degenerative diseases
  • hormonal imbalance
  • anti-inflammatory activity
  • multi-targeting compounds

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Published Papers (3 papers)

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Research

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19 pages, 653 KB  
Article
Butylated Hydroxytoluene (BHT) and p-Coumaric Acid Conjugates of Dipeptide Proline and GABA as Multi-Functional Agents with High Pharmacological Potential
by Georgios Papagiouvannis, Panagiotis Theodosis-Nobelos and Eleni A. Rekka
Molecules 2026, 31(8), 1323; https://doi.org/10.3390/molecules31081323 - 17 Apr 2026
Viewed by 207
Abstract
Oxidative stress and inflammation are interconnected pathological processes involved in the progression of neurodegenerative, cardiovascular, and metabolic diseases, highlighting the need for multifunctional therapeutic agents targeting multiple pathways. In this study, two novel hybrid compounds were designed and synthesized in three steps by [...] Read more.
Oxidative stress and inflammation are interconnected pathological processes involved in the progression of neurodegenerative, cardiovascular, and metabolic diseases, highlighting the need for multifunctional therapeutic agents targeting multiple pathways. In this study, two novel hybrid compounds were designed and synthesized in three steps by conjugating butylated phenolic moieties derived from butylated hydroxytoluene and p-coumaric acid with proline and γ-aminobutyric acid (GABA). The aim was the combination of antioxidant, anti-inflammatory, and cytoprotective properties within a single molecular framework. The compounds were evaluated using a comprehensive panel of in vitro and in vivo assays to assess antioxidant, metal-reducing, iron-chelating, antiglycation, anti-inflammatory, and acetylcholinesterase inhibitory activities. Both compounds exhibited significant antioxidant activity, with compound 2 demonstrating superior radical scavenging ability against DPPH, ABTS·+ and hydrogen peroxide (IC50 86 μM, 25 μM and 104 μM, respectively), enhanced ferric-reducing capacity (up to 91% of trolox activity), and strong iron-chelating activity (61.3%). Compound 2 also showed potent inhibition of lipid peroxidation (IC50 17.5 μM) and moderate antiglycation effects (44%), indicating substantial cytoprotective potential. Furthermore, both compounds selectively inhibited COX-2 over COX-1 and demonstrated moderate lipoxygenase inhibition, while compound 2 exhibited significant in vivo anti-inflammatory activity (53%), exceeding that of ibuprofen. Moderate acetylcholinesterase inhibition was also observed. In summary, the results confirm the design rationale, indicating that compound 2 could be further optimized as a multi-targeting molecule directed against oxidative stress- and inflammation-mediated conditions. Full article
(This article belongs to the Special Issue Oxidative Stress and Antioxidants in Degenerative Conditions)
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Review

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34 pages, 939 KB  
Review
Biochemical Mechanisms of Cellular Stress Adaptation in the Pathogenesis of Chronic Diseases
by Joanna Lemanowicz, Sylwester M. Kloska, Anetta Siwik-Ziomek, Paweł Kołaczyk, Urszula Wnuk Lipińska and Anna Kloska
Molecules 2026, 31(9), 1381; https://doi.org/10.3390/molecules31091381 - 22 Apr 2026
Viewed by 414
Abstract
Chronic diseases increasingly reflect a shared biological origin: persistent cellular stress. This review summarizes the biochemical mechanisms that normally preserve cellular homeostasis, namely redox regulation, endoplasmic reticulum proteostasis, mitochondrial quality control, autophagy, and DNA damage response, and explains how they fail under sustained [...] Read more.
Chronic diseases increasingly reflect a shared biological origin: persistent cellular stress. This review summarizes the biochemical mechanisms that normally preserve cellular homeostasis, namely redox regulation, endoplasmic reticulum proteostasis, mitochondrial quality control, autophagy, and DNA damage response, and explains how they fail under sustained lifestyle-related overload. Repeated exposure to psychological stress, sleep disruption, hypercaloric intake, and physical inactivity shifts adaptive signaling toward maladaptation, promoting oxidative damage, protein misfolding, mitochondrial dysfunction, low-grade inflammation, and genomic instability. These interconnected processes contribute to the development and progression of major chronic non-communicable diseases, including obesity, type 2 diabetes, cardiovascular disease, neurodegeneration, and cancer. Particular emphasis is placed on circadian and neuroendocrine regulation, especially overactivation of the hypothalamic–pituitary–adrenal axis and impaired nocturnal regenerative pathways such as glymphatic clearance and DNA repair. Together, the evidence supports a unifying model in which chronic pathology emerges from cumulative failure of cellular resilience systems rather than isolated organ-specific defects. This perspective highlights sleep optimization, stress reduction, and metabolic regulation as mechanistically grounded strategies for prevention and supportive interventions for chronic disease. Full article
(This article belongs to the Special Issue Oxidative Stress and Antioxidants in Degenerative Conditions)
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30 pages, 1702 KB  
Review
Summarizing the Role of Selected Adipokines in Parkinson’s Disease: What Is Known About Leptin, Adiponectin, Resistin, Visfatin, and Progranulin in Neurodegeneration?
by Jan Milanowski, Marta Pawłowska, Alina Woźniak and Karolina Szewczyk-Golec
Molecules 2025, 30(22), 4431; https://doi.org/10.3390/molecules30224431 - 16 Nov 2025
Cited by 1 | Viewed by 1135
Abstract
Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide. It is characterized by the accumulation of α-synuclein, and its symptoms arise from the loss of dopaminergic neurons in the substantia nigra, contributing to the development of both motor (MS) and non-motor [...] Read more.
Parkinson’s disease (PD) is the second most common neurodegenerative disease worldwide. It is characterized by the accumulation of α-synuclein, and its symptoms arise from the loss of dopaminergic neurons in the substantia nigra, contributing to the development of both motor (MS) and non-motor (NMS) symptoms. The detailed pathomechanism of the disease progression is unknown, although microglia activation and ongoing neuroinflammation are thought to play key roles. It is known that adipokines have a wide-ranging impact on various processes, including those implicated in PD. We have analyzed a series of studies regarding the significance and involvement of leptin, adiponectin, resistin, visfatin, and progranulin in neurodegeneration. Available evidence suggests that adipokines modulate PD pathology through their effects on inflammation, oxidative stress, or α-synuclein accumulation. Thus, the examined adipokines may serve as potential targets for PD treatment or as biomarkers of disease progression. Full article
(This article belongs to the Special Issue Oxidative Stress and Antioxidants in Degenerative Conditions)
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